Abstract 215P
Background
Almost 60% of breast cancers (BCs) diagnosed in germline BRCA1/2 pathogenic variants (gBRCAm) carriers are HR+/HER2-. CDK4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET) represent standard first-line treatment for HR+/HER2- metastatic BC. Sparse data suggest limited CDK4/6i benefit among gBRCAm carriers. However, prespecified subgroup analyses from pivotal trials are lacking, and current data quality is poor given the small patient populations.
Methods
We conducted a systematic review and meta-analysis of studies evaluating CDK4/6i outcomes in patients with HR+/HER2- metastatic BC according to gBRCA status. We queried Embase, MEDLINE, PubMed, ASCO, ESMO and SABCS proceedings to identify eligible studies. Progression free survival (PFS) and overall survival (OS) were compared according to gBRCA status (gBRCAm vs. gBRCA wild type [wt] and vs. a combined group of gBRCAwt patients and unknown status [wt/unk]).
Results
Of 1135 potentially eligible records, 11 studies were included in the meta-analysis, covering a population of 11516 patients, 392 of whom with gBRCAm (range 6-145). Two studies included only gBRCA tested patients; all other studies also allowed gBRCA untested patients. Five studies only assessed patients receiving CDK4/6i as fistr-line therapy. The meta-analysis of studies with available data for gBRCAm vs. gBRCAwt patients resulted in an HR for PFS of 1.72 (95%CI 1.29-2.27) and an HR for OS of 2.02 (95%CI 1.36-3.01). Expanding the analysis with the inclusion of patients with unknown gBRCA status led to similar results (gBRCAm vs. gBRCAwt/unk), with an HR for PFS of 2.21 (95%CI 1.62-3.03) and for OS of 1.65 (95%CI 1.16-2.34). A sensitivity analysis of patients receiving CDK4/6i as fistr-line showed similar results, with gBRCAm patients having a worse PFS (HR 4.12, 95%CI 1.82-9.35) and OS (HR 1.97, 95%CI 0.62-6.22) compared to gBRCAwt/unk.
Conclusions
gBRCAm patients with advanced HR+/HER2- BC treated with CDK4/6i + ET present a significant worse PFS and OS, with a doubling in risk of death compared to gBRCAwt. Further research is needed to understand molecular mechanisms and identify the optimal treatment sequence.
Clinical trial identification
CRD42024500780 (22 Jan 2024).
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
F. Miglietta: Financial Interests, Personal, Invited Speaker: Roche, Novartis, Seagen, Pfizer, Lilly, Menarini; Financial Interests, Personal, Advisory Board: AstraZeneca, MSD. M.V. Dieci: Financial Interests, Personal, Invited Speaker: Eli Lilly, Exact sciences, Gilead, Seagen, Daiichi Sankyo, Novartis; Financial Interests, Personal, Advisory Board: Novartis, Eli Lilly, Seagen, Exact Science, Daiichi Sankyo, Gilead; Financial Interests, Personal, Other, Consultancy: Pfizer; Financial Interests, Personal, Other, Consultancy on educational project: Roche. G. Griguolo: Financial Interests, Personal, Invited Speaker: Novartis, Eli Lilly, MSD; Financial Interests, Personal, Advisory Board: Gilead, Menarini, Seagen; Other, Travel Support: Novartis, Amgen, Daiichi Sankyo, Eli Lilly, Gilead; Other, Trave Support: Pfizer. F. Girardi: Financial Interests, Personal, Invited Speaker: AstraZeneca, Eli Lilly, Gilead Scince; Financial Interests, Personal, Other, Travel support: Eli Lilly; Financial Interests, Other, Travel Support: Gilead Science. V. Guarneri: Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, GSK, AstraZeneca, Gilead, Exact Sciences; Financial Interests, Personal, Advisory Board: Eli Lilly, Novartis, MSD, Gilead, Merck, Exact Sciences, Eisai, Olema Oncology, AstraZeneca, Daiichi Sankyo, Pfizer; Financial Interests, Personal, Expert Testimony: Eli Lilly; Financial Interests, Institutional, Invited Speaker: Eli Lilly, Roche, BMS, Novartis, AstraZeneca, MSD, Synton Biopharmaceuticals, Merck, GSK, Daiichi Sankyo, Nerviano, Pfizer; Non-Financial Interests, Member: ASCO. All other authors have declared no conflicts of interest.